Functional electrical stimulation (FES) is a biomedical therapy by which electrical stimulation is applied to peripheral nerves to artificially generate muscle activation. Robotic assisted treadmill training is a separately developed therapy by which a motorized system powers leg orthoses to move a spinal cord injury (SCI) patient's legs in a trajectory designed to mimic walking while the body weight is supported by a harness. The potential benefits of combining the two technologies have not been explored. Current FES technology is designed to merely supply the muscle activation that would otherwise be absent or weakened in SCI patients. It relies on imprecisely controlled timing usually based on the onset of a detected event, such as heel strike, and typically results in abnormal gait patterns and quick onset of fatigue. In contrast, the proposed novel FES system is designed to enhance spinal circuitry capable of generating a more natural gait. An FES system will be developed to time stimulation to robotically controlled movements in complete spinal cord transected (ST) rodents so that the neural pathways between the spinal cord and muscles will be stimulated at appropriate times to reinforce spinal circuits. After integrating robotic control with FES, the therapeutic benefits will be measured in ST rodents. Animals will be implanted with electrodes to record electrical activity from the ankle flexor and extensor muscles (EMG) and to stimulate innervating nerves. Resulting kinematics, kinetics, and EMG will be compared in rats receiving FES integrated with robotic control and conventional FES, which is timed according to typical gait patterns rather than robot- controlled movements. Finally, stimulation parameters will be adjusted to assist only as needed; in particular, stimulation will be reduced with improved performance, as determined from changes in kinematics and EMG. This adaptive therapy is expected to lead to less reliance on artificial means and greater restoration of control to spinal circuitry, ultimately resulting in a more natural and efficient gait. The proposed project is designed first to enhance the health of spinal cord injury patients by improving on existing therapies. It will also advance our understanding of the interaction between applied electrical stimulation and the human nervous system, which will in turn advance the development of existing therapies to impact a range of neurological disorders. PUBLIC HEALTH RELEVANCE: Lack of mobility severely worsens the health and quality of life for spinal cord injury patients. An existing therapy (functional electrical stimulation) will be innovatively modified to train the injured spinal cord to resume control over locomotion and rely less on artificial externally provided control. The proposed research is expected to lead to a more effective and useable technology for rehabilitating locomotor skills.